Circulating Tumor Cells: Who is the Killer?

This article is a critical note on the subject of Circulating Tumor Cells (CTC). It takes into account the tumor identity of Circulating Tumor Cells as cancer seeds in transit from primary to secondary soils, rather than as a "biomarker", and considers the help this field could bring to cancer patients. It is not meant to duplicate information already available in a large number of reviews, but to stimulate considerations, further studies and development helping the clinical use of tumor cells isolated from blood as a modern personalized, non-invasive, predictive test to improve cancer patients' life. The analysis of CTC challenges, methodological bias and critical issues points out to the need of referring to tumor cells extracted from blood without any bias and identified by cytopathological diagnosis as Circulating Cancer Cells (CCC). Finally, this article highlights recent developments and identifies burning questions which should be addressed to improve our understanding of the domain of CCC and their potential to change the clinical practice.